Clinical relevance of different IgG and IgM serum antibody responses to Borrelia burgdorferi after antibiotic therapy for erythema migrans: long-term follow-up study of 113 patients.

OBJECTIVES To investigate the kinetics of anti-Borrelia burgdorferi antibodies for a minimum of 1 year after antibiotic therapy in patients with erythema migrans (EM) and to correlate antibody titer kinetics with clinical variables. DESIGN Retrospective study of serial anti-B burgdorferi antibodies in correlation to clinical variables. SETTING University-based hospital. PATIENTS One hundred thirteen patients with EM. INTERVENTIONS Pretreatment and a median of 4 consecutive posttreatment serum samples from median follow-up of more than 400 days were simultaneously investigated for anti-B burgdorferi IgG and IgM antibodies. Semiquantitative titers were plotted to identify different groups of antibody kinetics. Individual patients were then stratified to those groups according to their antibody development. A statistical comparison of clinical and therapy-related characteristics among the serologic groups was performed. RESULTS Anti-B burgdorferi IgG and IgM antibody titers developed in 3 distinct courses: persistent positivity across follow-up (IgG: 12 patients, 11%; IgM: 14, 12%), persistent negativity (IgG: 63, 56%; IgM: 47, 42%), and decrease of a positive pretreatment titer to a negative titer approximately 5 months after therapy (IgG: 34, 30%; IgM: 49, 43%). Statistics revealed significant correlations only between persistent positive IgG titers and long disease duration or large EM lesions before therapy. CONCLUSIONS Long duration or large size of EM before therapy correlates with persistence of a positive anti- B burgdorferi IgG antibody titer after therapy. Serologic profiles do not depend on the type or duration of therapy or the clinical course thereafter. Thus, antibody testing in the follow-up of patients with EM is inappropriate for the assessment of therapeutic response.

[1]  A. Lebech,et al.  Improved immunoglobulin M serodiagnosis in Lyme borreliosis by using a mu-capture enzyme-linked immunosorbent assay with biotinylated Borrelia burgdorferi flagella , 1991, Journal of clinical microbiology.

[2]  A. Steere,et al.  Treatment of the early manifestations of Lyme disease. , 1983, Annals of internal medicine.

[3]  R. Nadelman,et al.  Comparison of Culture-Confirmed Erythema Migrans Caused by Borrelia burgdorferi sensu stricto in New York State and by Borrelia afzelii in Slovenia , 1999, Annals of Internal Medicine.

[4]  R Ruthazer,et al.  Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10-20 years after active Lyme disease. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  R. Nadelman,et al.  Long-term follow-up of patients with culture-confirmed Lyme disease. , 2003, The American journal of medicine.

[6]  N. Pedersen,et al.  Measurement of antibodies to the Borrelia burgdorferi flagellum improves serodiagnosis in Lyme disease , 1988, Journal of clinical microbiology.

[7]  M. Kramer,et al.  Antigenic Variability of Borrelia burgdorferi , 1988, Annals of the New York Academy of Sciences.

[8]  R. Nadelman,et al.  The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. , 1996, The American journal of medicine.

[9]  A. Steere,et al.  The early clinical manifestations of Lyme disease. , 1983, Annals of internal medicine.

[10]  J. Halperin,et al.  Seronegative Lyme disease. Dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi. , 1989, The New England journal of medicine.

[11]  L. Bennet,et al.  Clinical Outcome of Erythema Migrans After Treatment with Phenoxymethyl Penicillin , 2003, Scandinavian journal of infectious diseases.

[12]  F. Strle,et al.  Azithromycin and doxycycline for treatment ofBorrelia culture-positive erythema migrans , 2005, Infection.

[13]  B. Dijkmans,et al.  Long-term prognosis in patients treated for erythema chronicum migrans and acrodermatitis chronica atrophicans. , 1997, Archives of dermatology.

[14]  P. Duray,et al.  The Long-Term Clinical Outcomes of Lyme Disease: A Population-Based Retrospective Cohort Study , 1994, Annals of Internal Medicine.

[15]  F. Strle,et al.  European Lyme borreliosis: 231 culture-confirmed cases involving patients with erythema migrans. , 1996, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[16]  H. Kerl,et al.  No detection of Borrelia burgdorferi-specific DNA in erythema migrans lesions after minocycline treatment. , 1995, Archives of dermatology.

[17]  B. Hederstedt,et al.  Serologic studies of erythema chronicum migrans Afzelius and acrodermatitis chronica atrophicans with indirect immunofluorescence and enzyme-linked immunosorbent assays. , 1985, Acta dermato-venereologica.

[18]  F. Breier,et al.  Erythema migrans and serodiagnosis by enzyme immunoassay and immunoblot with three borrelia species. , 1999, Wiener klinische Wochenschrift.

[19]  G. Stanek,et al.  European Union Concerted Action on Risk Assessment in Lyme Borreliosis: clinical case definitions for Lyme borreliosis. , 1996, Wiener klinische Wochenschrift.

[20]  A. Steere Lyme disease. , 1989, The New England journal of medicine.

[21]  A. Steere,et al.  Practice guidelines for the treatment of Lyme disease. The Infectious Diseases Society of America. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  M. Gerber,et al.  Persistence of serum antibodies to Borrelia burgdorferi in patients treated for Lyme disease. , 1992, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  B. W. Berger,et al.  Failure of Borrelia burgdorferi to survive in the skin of patients with antibiotic-treated Lyme disease. , 1992, Journal of the American Academy of Dermatology.

[24]  K. Hansen,et al.  Serodiagnosis of erythema migrans and acrodermatitis chronica atrophicans by the Borrelia burgdorferi flagellum enzyme-linked immunosorbent assay , 1989, Journal of clinical microbiology.

[25]  B. Luft,et al.  Lyme borreliosis. , 1994, International journal of antimicrobial agents.

[26]  A. Steere,et al.  Clinical Characteristics and Treatment Outcome of Early Lyme Disease in Patients with Microbiologically Confirmed Erythema Migrans , 2002, Annals of Internal Medicine.

[27]  R. Nadelman,et al.  Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans , 1996, Journal of clinical microbiology.

[28]  B. Wilske,et al.  Antibiotic Therapy of Early European Lyme Borreliosis and Acrodermatitis Chronica Atrophicans , 1988, Annals of the New York Academy of Sciences.

[29]  Antonio Lanzavecchia,et al.  Maintenance of Serological Memory by Polyclonal Activation of Human Memory B Cells , 2002, Science.

[30]  K. Weber,et al.  Treatment failure in erythema migrans — a review , 2005, Infection.

[31]  B. Wilske,et al.  A randomized trial of ceftriaxone versus oral penicillin for the treatment of early european lyme borreliosis , 1990, Infection.

[32]  F. Strle,et al.  A two year prospective study to compare culture and polymerase chain reaction amplification for the detection and diagnosis of Lyme borreliosis. , 1997, Molecular pathology : MP.

[33]  E. Åsbrink Cutaneous manifestations of Lyme borreliosis. Clinical definitions and differential diagnoses. , 1991, Scandinavian journal of infectious diseases. Supplementum.

[34]  J. Benach,et al.  Isolation of antigenic components from the Lyme disease spirochete: their role in early diagnosis. , 1987, The Journal of infectious diseases.

[35]  H. Lomholt,et al.  Long-term serological follow-up of patients treated for chronic cutaneous borreliosis or culture-positive erythema migrans. , 2000, Acta dermato-venereologica.

[36]  B. Svenungsson,et al.  Serological follow-up after treatment of patients with erythema migrans and neuroborreliosis , 1994, Journal of clinical microbiology.

[37]  F. Strle,et al.  Epidemiology of Lyme Borreliosis , 1993 .

[38]  R. Mullegger Dermatological manifestations of Lyme borreliosis. , 2004, European journal of dermatology : EJD.

[39]  A. Steere,et al.  The T-cell proliferative assay in the diagnosis of Lyme disease. , 1991, Annals of internal medicine.

[40]  H. Soini,et al.  Early dissemination of Borrelia burgdorferi without generalized symptoms in patients with erythema migrans Note , 2001, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[41]  D. Lipsker,et al.  How accurate is a clinical diagnosis of erythema chronicum migrans? Prospective study comparing the diagnostic accuracy of general practitioners and dermatologists in an area where lyme borreliosis is endemic. , 2004, Archives of dermatology.

[42]  C H Schmid,et al.  Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. , 2001, The New England journal of medicine.

[43]  S. Malawista,et al.  Lyme disease: recommendations for diagnosis and treatment. , 1991, Annals of internal medicine.